General Information of Drug Therapeutic Target (DTT) (ID: TT8NBXR)

DTT Name Integrin beta-3 (ITGB3)
Synonyms GPIIIa; GP3A; CD61
Gene Name ITGB3
DTT Type
Literature-reported target
[1]
BioChemical Class
Integrin
UniProt ID
ITB3_HUMAN
TTD ID
T26457
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MRARPRPRPLWATVLALGALAGVGVGGPNICTTRGVSSCQQCLAVSPMCAWCSDEALPLG
SPRCDLKENLLKDNCAPESIEFPVSEARVLEDRPLSDKGSGDSSQVTQVSPQRIALRLRP
DDSKNFSIQVRQVEDYPVDIYYLMDLSYSMKDDLWSIQNLGTKLATQMRKLTSNLRIGFG
AFVDKPVSPYMYISPPEALENPCYDMKTTCLPMFGYKHVLTLTDQVTRFNEEVKKQSVSR
NRDAPEGGFDAIMQATVCDEKIGWRNDASHLLVFTTDAKTHIALDGRLAGIVQPNDGQCH
VGSDNHYSASTTMDYPSLGLMTEKLSQKNINLIFAVTENVVNLYQNYSELIPGTTVGVLS
MDSSNVLQLIVDAYGKIRSKVELEVRDLPEELSLSFNATCLNNEVIPGLKSCMGLKIGDT
VSFSIEAKVRGCPQEKEKSFTIKPVGFKDSLIVQVTFDCDCACQAQAEPNSHRCNNGNGT
FECGVCRCGPGWLGSQCECSEEDYRPSQQDECSPREGQPVCSQRGECLCGQCVCHSSDFG
KITGKYCECDDFSCVRYKGEMCSGHGQCSCGDCLCDSDWTGYYCNCTTRTDTCMSSNGLL
CSGRGKCECGSCVCIQPGSYGDTCEKCPTCPDACTFKKECVECKKFDRGALHDENTCNRY
CRDEIESVKELKDTGKDAVNCTYKNEDDCVVRFQYYEDSSGKSILYVVEEPECPKGPDIL
VVLLSVMGAILLIGLAALLIWKLLITIHDRKEFAKFEEERARAKWDTANNPLYKEATSTF
TNITYRGT
Function
Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. Fibrinogen binding enhances SELP expression in activated platelets. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling. ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling. ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling. ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling. ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling. ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGAV:ITGB3 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1. Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor.
KEGG Pathway
Rap1 signaling pathway (hsa04015 )
Phagosome (hsa04145 )
PI3K-Akt signaling pathway (hsa04151 )
Osteoclast differentiation (hsa04380 )
Focal adhesion (hsa04510 )
ECM-receptor interaction (hsa04512 )
Platelet activation (hsa04611 )
Neutrophil extracellular trap formation (hsa04613 )
Hematopoietic cell lineage (hsa04640 )
Regulation of actin cytoskeleton (hsa04810 )
Thyroid hormone signaling pathway (hsa04919 )
Human cytomegalovirus infection (hsa05163 )
Human papillomavirus infection (hsa05165 )
Herpes simplex virus 1 infection (hsa05168 )
Proteoglycans in cancer (hsa05205 )
MicroRNAs in cancer (hsa05206 )
Hypertrophic cardiomyopathy (hsa05410 )
Arrhythmogenic right ventricular cardiomyopathy (hsa05412 )
Dilated cardiomyopathy (hsa05414 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
Elastic fibre formation (R-HSA-1566948 )
PECAM1 interactions (R-HSA-210990 )
Molecules associated with elastic fibres (R-HSA-2129379 )
Integrin cell surface interactions (R-HSA-216083 )
TGF-beta receptor signaling activates SMADs (R-HSA-2173789 )
Syndecan interactions (R-HSA-3000170 )
ECM proteoglycans (R-HSA-3000178 )
Integrin signaling (R-HSA-354192 )
GRB2 (R-HSA-354194 )
p130Cas linkage to MAPK signaling for integrins (R-HSA-372708 )
VEGFA-VEGFR2 Pathway (R-HSA-4420097 )
Signal transduction by L1 (R-HSA-445144 )
MAP2K and MAPK activation (R-HSA-5674135 )
Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946 )
Signaling by high-kinase activity BRAF mutants (R-HSA-6802948 )
Signaling by BRAF and RAF1 fusions (R-HSA-6802952 )
Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955 )
Signaling downstream of RAS mutants (R-HSA-9649948 )
Signaling by RAF1 mutants (R-HSA-9656223 )
Platelet degranulation (R-HSA-114608 )

References

1 The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res. 2008 Oct 1;68(19):7711-7.